crossing96/oncoscreening huggingface dataset:
Female sexual function evaluation and intraoperative vaginal reconstruction in bladder cancer.	RC significantly negatively impacts sexual function (SF) in both men and women. While significant research resources have been allocated to examine the deleterious effects of post prostatectomy erectile dysfunction, little attention has been directed towards female sexual function and organ preservation post cystectomy. These academic shortcomings often result in poor provider awareness and inadequate preoperative assessment. As such, it is crucial for all providers involved in female RC care to understand the necessary and available tools for preoperative evaluation, in addition to the anatomic and reconstructive techniques. This review aims to summarize the current preoperative evaluation and available tools of SF assessment and describe in detail the varying operative techniques in the preservation or restoration of SF in women after RC. The review explores the intricacies of preoperative evaluation tools, and intraoperative techniques for organ- and nerve-sparing during radical cystectomy in females. Particular emphasis on vaginal reconstruction after partial or complete resection is provided, including split-thickness skin (STF) graft vaginoplasy, pedicled flaps, myocutaneous flaps and use of bowel segments. In conclusion, this narrative review highlights the importance of understanding anatomic considerations and nerve-sparing strategies in promoting postoperative SF and quality of life. Furthermore, the review describes the advantages and limitations of each organ- and nerve-sparing technique and their impact on sexual function and overall well-being.	bladder
Effect of decreased renal function on poor oncological outcome after radical cystectomy.	PURPOSE: To evaluate the impact of preoperative renal impairment on the oncological outcomes of patients with urothelial carcinoma who underwent radical cystectomy. MATERIALS AND METHODS: We retrospectively reviewed the medical records of patients with urothelial carcinoma who underwent radical cystectomy from 2004 to 2017. All patients who underwent preoperative (99m)Tc-diethylenetriaminepentaacetic acid renal scintigraphy (DTPA) were identified. We divided the patients into two groups according to their glomerular filtration rates (GFRs): GFR group 1, GFR≥90 mL/min/1.73 m²; GFR group 2, 60≤GFR<90 mL/min/1.73 m². We included 89 patients in GFR group 1 and 246 patients in GFR group 2 and compared the clinicopathological characteristics and oncological outcomes between the two groups. RESULTS: The mean time required for recurrence was 125.5±8.0 months in GFR group 1 and 85.7±7.4 months in GFR group 2 (p=0.030). The mean cancer-specific survival was 131.7±7.8 months in GFR group 1 and 95.5±6.9 months in GFR group 2 (p=0.051). The mean overall survival was 123.3±8.1 months in GFR group 1 and 79.5±6.6 months in GFR group 2 (p=0.004). CONCLUSIONS: Preoperative GFR values in the range of 60≤GFR<90 mL/min/1.73 m² are independent prognostic factors for poor recurrence-free survival, cancer-specific survival, and overall survival in patients after radical cystectomy compared with GFR values of ≥90 mL/min/1.73 m².	bladder
Long-term Outcomes from a Phase 2 Study of Neoadjuvant Chemotherapy for Muscle-invasive Bladder Cancer (SWOG S1314; NCT02177695).	BACKGROUND: The COXEN gene expression model was evaluated for prediction of response to neoadjuvant chemotherapy for muscle-invasive bladder cancer (MIBC). OBJECTIVE: To conduct a secondary analysis of the association of each COXEN score with event-free survival (EFS) and overall survival (OS) and by treatment arm. DESIGN, SETTING, AND PARTICIPANTS: This was a randomized phase 2 trial of neoadjuvant gemcitabine-cisplatin (GC) or dose-dense methotrexate-vinblastine-adriamycin-cisplatin (ddMVAC) in MIBC. INTERVENTION: Patients were randomized to ddMVAC (every 14 d) or GC (every 21 d), both for four cycles. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: EFS events were defined as progression or death before scheduled surgery, a decision to not undergo surgery, recurrence, or death due to any cause after surgery. Cox regression was used to evaluate the COXEN score or treatment arm association with EFS and OS. RESULTS AND LIMITATIONS: A total of 167 evaluable patients were included in the COXEN analysis. The COXEN scores were not significantly prognostic for OS or EFS in the respective arms, but the GC COXEN score had a hazard ratio (HR) of 0.45 (95% confidence interval [CI] 0.20-0.99; p = 0.047) when the arms were pooled. In the intent-to-treat analysis (n = 227), there was no significant difference between ddMVAC and GC for OS (HR 0.87, 95% CI 0.54-1.40; p = 0.57) or EFS (HR 0.86, 95% CI 0.59-1.26; p = 0.45). Among the 192 patients who underwent surgery, pathologic response (pT0 vs downstaging vs no response) was strongly correlated with superior postsurgical survival (5-yr OS 90%, 89% and 52%, respectively). CONCLUSIONS: The COXEN GC score has prognostic value for patients receiving cisplatin-based neoadjuvant treatment. The randomized, prospective design provides estimates of OS and EFS for GC and ddMVAC in this population. Pathologic response (<pT2) performed well as an intermediate endpoint in this modern cohort. For expediency in evaluating new regimens, pathologic response should continue to be used in phase 2 trials. PATIENT SUMMARY: In this study, we evaluated a biomarker to predict the response to chemotherapy. The results did not meet the preset study parameters, but our study provides information on clinical outcomes with the use of chemotherapy before surgery for bladder cancer.	bladder
[Preoperative chemotherapy for patients with upper tract urothelial carcinoma: Impact on renal function].	PURPOSE: Upper tract urothelial carcinoma (UTUC) are rare tumors with a poor prognosis. The standard treatment for localized disease is based on total nephroureterectomy (NUT) followed by platinum-based adjuvant chemotherapy for eligible patients at risk of recurrence. However, many patients have renal failure after surgery preventing chemotherapy. Thus, the place of preoperative chemotherapy (POC) is questioned with little information available about renal toxicity and efficacity. METHODS: A single center retrospective study was performed on patients with UTUC who received POC. RESULTS: In all, 24 patients with localized UTUC were treated with POC between 2013 and 2022. Twenty-one (91%) had secondarily NUT. In this cohort, POC did not result in degradation of median renal function (pre-POC median GFR: 70mL/min, post-POC median GFR: 77mL/min, P=0.79), unlike NUT (post-NUT median GFR: 51.5mL/min, P<0.001). In addition, the rate of complete pathological response to pathological examination was 29%. After a median follow-up of 27.4 months, the overall survival rate was 74% and the recurrence-free survival rate was 46%. CONCLUSION: POC for UTUC shows a very reassuring renal toxicity profile and encouraging histological results. These data encourage prospective studies assessing its place for UTUC management.	bladder
Analysis of ICAM-1 Expression on Bladder Carcinoma Cell Lines and Infectivity and Oncolysis by Coxsackie Virus A21.	Oncolytic viruses are biological agents which can easily be delivered at high doses directly to the bladder through a catheter (intravesical), with low risk of systemic uptake and toxicity. To date, a number of viruses have been delivered intravesically in patients and in murine models with bladder cancer and antitumour effects demonstrated. Here, we describe in vitro methods to evaluate Coxsackie virus, CVA21, as an oncolytic virus for the treatment of human bladder cancer by determining the susceptibility of bladder cancer cell lines expressing differing levels of ICAM-1 surface receptor to CVA21.	bladder
Assessment of PD-L1 Status in Urothelial Cancer.	Since 2016, the immunotherapeutic agents targeting PD-1 and PD-L1 are an integral part in first-line and second-line treatment of advanced or metastatic urothelial cancer. By PD-1 and PD-L1 inhibition with these drugs, the immune system is supposed to regain the capacity to actively kill cancer cells. Meanwhile, PD-L1 assessment is prescribed for patients not being eligible for platinum-based chemotherapy in first-line settings in metastatic disease (for monotherapy with atezolizumab or pembrolizumab) and for patients who are intended to receive adjuvant nivolumab treatment following radical cystectomy. Several challenges which are highlighted in this chapter affect PD-L1 testing in daily routine including availability of representative tissue materials, inter-observer variability, and different available PD-L1 immunohistochemistry assays with different analytical properties.	bladder
Considering the Effects of Modern Point-of-Care Urine Biomarker Assays in Follow-Up of Patients with High-Risk Non-muscle-Invasive Bladder Cancer.	"BACKGROUND: Although a plethora of urine markers for diagnosis and follow-up of patients with bladder cancer (BC) has been developed and studied, the clinical impact of urine testing on patient management remains unclear. The goal of this manuscript is to identify scenarios for a potential use of modern point-of-care (POC) urine marker assays in the follow-up of patients with high-risk non-muscle-invasive BC (NMIBC) and estimate potential risks and benefits. METHODS: To permit comparison between different assays, the results of 5 different POC assays studied in a recent prospective multicenter study including 127 patients with suspicious cystoscopy undergoing TURB were used for this simulation. For the current standard of care (SOC), a ""marker-enforced"" procedure, and a combined strategy sensitivity (Se), estimated number of cystoscopies, and the numbers needed to diagnose (NND) over a 1-year follow-up period were calculated. RESULTS: For regular cystoscopy (SOC), a Se of 91.7% and a NND of 42.2 repetitive office cystoscopies (WLCs) for 1 recurrent tumor at 1 year were calculated. For the ""marker-enforced"" strategy, marker sensitivities between 94.7% and 97.1% were observed. The ""combined"" strategy yielded for markers with a Se exceeding 50% an overall Se at 1 year similar or superior to the current SOC. Savings regarding the number of cystoscopies in the ""marker-enforced"" strategy vs. the SOC were small, while, depending on the marker, up to 45% of all cystoscopies may be saved using the ""combined"" strategy. CONCLUSIONS: Based on the results of this simulation, a marker-supported follow-up of patients with high-risk (HR) NMIBC is safe and offers options to significantly reduce the number of cystoscopies without compromising the Se. Further research focusing on prospective randomized trials is needed to finally find a way to include marker results into clinical decision-making."	bladder
NGS-Based Tumor-Informed Analysis of Circulating Tumor DNA.	Accurate circulating tumor DNA (ctDNA) detection has an immense biomarker potential in all phases of the cancer disease course. Presence of ctDNA in the blood has been shown to have prognostic value in various cancer types as it may reflect the actual tumor burden. There are two main methods to consider, a tumor-informed and a tumor-agnostic analysis of ctDNA. Both techniques exploit the short half-life of circulating cell-free DNA (cfDNA)/ctDNA for disease monitoring and ultimately future clinical treatment intervention. Urothelial carcinoma is characterized by a high mutation spectrum but very few hotspot mutations. This limits tumor agnostic usability of hotspot mutation or fixed sets of genes for ctDNA detection. Here we focus on a tumor-informed analysis for ultrasensitive patient- and tumor-specific ctDNA detection using personalized mutation panels, probes that bind to specific genomic sequences to enrich for the region of interest. In this chapter, we describe methods for purification of high-quality cfDNA and guidelines for designing tumor-informed customized capture panels for sensitive detection of ctDNA. Furthermore, a detailed protocol for library preparation and panel capture utilizing a double enrichment strategy with low amplification is described.	bladder
Identification of STAG2-Mutant Bladder Cancers by Immunohistochemistry.	Bladder cancer is the fifth most common cancer in the United States. Most bladder cancers are early-stage lesions confined to the mucosa or submucosa and are therefore classified as non-muscle-invasive bladder cancer (NMIBC). A minority of tumors are diagnosed after they have invaded the underlying detrusor muscle and are classified as muscle-invasive bladder cancer (MIBC). Mutational inactivation of the STAG2 tumor suppressor gene is common in bladder cancer, and we and others have recently demonstrated that STAG2 mutation status can be used as an independent prognostic biomarker to predict whether NMIBC will recur and/or progress to MIBC. Here we describe an immunohistochemistry-based assay for identifying the STAG2 mutational status of bladder tumors.	bladder
Using Sister Chromatid Exchange Assay to Detect Homologous Recombination Deficiency in Epigenetically Deregulated Urothelial Carcinoma Cells.	Sister chromatid exchange (SCE) is the process of exchanging regions between two sister chromatids during DNA replication. Exchanges between replicated chromatids and their sisters can be visualized in cells when DNA synthesis in one chromatid is labelled by 5-bromo-2'-deoxyuridine (BrdU). Homologous recombination (HR) is considered as the principal mechanism responsible for the sister chromatid exchange (SCE) upon replication fork collapse, and therefore SCE frequency upon genotoxic conditions reflects the capacity of HR repair to respond to replication stress. During tumorigenesis, inactivating mutations or altered transcriptome can affect a plethora of epigenetic factors that participate in DNA repair processes, and there are an increasing number of reports which demonstrate a link between epigenetic deregulation in cancer and homologous recombination deficiency (HRD). Therefore, the SCE assay can provide valuable information regarding the HR functionality in tumors with epigenetic deficiencies. In this chapter, we provide a method to visualize SCEs. The technique outlined below is characterized by high sensitivity and specificity and has been successfully applied to human bladder cancer cell lines. In this context, this technique could be used to characterize the dynamics of HR repair in tumors with deregulated epigenome.	bladder
A Drug Repurposing Pipeline Based on Bladder Cancer Integrated Proteotranscriptomics Signatures.	Delivering better care for patients with bladder cancer (BC) necessitates the development of novel therapeutic strategies that address both the high disease heterogeneity and the limitations of the current therapeutic modalities, such as drug low efficacy and patient resistance acquisition. Drug repurposing is a cost-effective strategy that targets the reuse of existing drugs for new therapeutic purposes. Such a strategy could open new avenues toward more effective BC treatment. BC patients' multi-omics signatures can be used to guide the investigation of existing drugs that show an effective therapeutic potential through drug repurposing. In this book chapter, we present an integrated multilayer approach that includes cross-omics analyses from publicly available transcriptomics and proteomics data derived from BC tissues and cell lines that were investigated for the development of disease-specific signatures. These signatures are subsequently used as input for a signature-based repurposing approach using the Connectivity Map (CMap) tool. We further explain the steps that may be followed to identify and select existing drugs of increased potential for repurposing in BC patients.	bladder
Scoring Systems for Immunohistochemistry in Urothelial Carcinoma.	Immunohistochemistry is widely used in diagnostic and scientific analysis of urothelial carcinoma. Objective interpretation of staining results is mandatory for accuracy and comparability in diagnostic and therapeutic patient care as well as research.Herein we summarize and explain standardized microscopic evaluation and scoring approaches for immunohistochemical stainings. We focus on commonly used and generally feasible approaches for different cellular compartments and comment on their utility in diagnostics and research practice.	bladder
Getting specific: participation preference in urooncological decision-making.	BACKGROUND: Shared decision-making is the gold standard for good clinical practice, and thus, psychometric instruments have been established to assess patients' generic preference for participation (e.g., the Autonomy Preference Index, API). However, patients' preferences may vary depending on the specific disease and with respect to the specific decision context. With a modified preference index (API-Uro), we assessed patients' specific participation preference in preference-sensitive decisions pertaining to urological cancer treatments and compared this with their generic participation preference. METHODS: In Study 1, we recruited (N = 469) urological outpatients (43.1% urooncological) at a large university hospital. Participation preference was assessed with generic measures (API and API case vignettes) and with the disease-specific API-Uro (urooncological case vignettes describing medical decisions of variable difficulty). A polychoric exploratory factor analysis was used to establish factorial validity and reduce items. In Study 2, we collected data from N = 204 bladder cancer patients in a multicenter study to validate the factorial structure with confirmatory factor analysis. Differences between the participation preference for different decision contexts were analyzed. RESULTS: Study 1: Scores on the specific urooncological case vignettes (API-Uro) correlated with the generic measure (r = .44) but also provided incremental information. Among the disease-specific vignettes of the API-Uro, there were two factors with good internal consistency (α ≥ .8): treatment versus diagnostic decisions. Patients desired more participation for treatment decisions (77.8%) than for diagnostic decisions (22%), χ(2)(1) = 245.1, p ≤ .001. Study 2: Replicated the correlation of the API-Uro with the API (r = .39) and its factorial structure (SRMR = .08; CFI = .974). Bladder cancer patients also desired more participation for treatment decisions (57.4%) than for diagnostic decisions (13.3%), χ²(1) =84, p ≤ .001. CONCLUSIONS: The desire to participate varies between treatment versus diagnostic decisions among urological patients. This underscores the importance of assessing participation preference for specific contexts. Overall, the new API-Uro has good psychometric properties and is well suited to assess patients' preferences. In routine care, measures of participation preference for specific decision contexts may provide incremental, allowing clinicians to better address their patients' individual needs.	bladder
Antibody Drug Conjugates in Bladder Cancer: Current Milestones and Future Perspectives.	Over the last several years, the treatment landscape of urothelial carcinoma has witnessed an unprecedented expansion of therapeutic options including checkpoint inhibitors, tyrosine kinase inhibitors, and antibody drug conjugates (ADC). Early trial data has shown that ADCs are safer and potentially effective treatment options in advanced bladder cancer as well as in the early disease. In particular, enfortumab-vedotin (EV) has shown promising results with a recent cohort of a clinical trial demonstrating that EV is effective as neoadjuvant monotherapy as well as in combination with pembrolizumab in metastatic setting. Similar promising results have been shown by other classes of ADC in other trials including sacituzumab-govitecan (SG) and oportuzumab monatox (OM). ADCs are likely to become a mainstay treatment option in the urothelial carcinoma playbook as either a monotherapy or combination therapy. The cost of the drug presents a real challenge, but further trial data may justify the use of the drug as mainstay treatment.	bladder
[Experience in the use of confocal laser endomicroscopy for the diagnosis of bladder papillary tumors].	INTRODUCTION: Visual confirmation of suspicious changes in the urinary tract mucosa is the cornerstone in the diagnosis of urothelial cancer. However, with bladder tumors, it is impossible to obtain histopathological data during cystoscopy both in white light and in photodynamic and narrow-spectrum modes, as well as with computerized chromoendoscopy. Confocal laser endomicroscopy (probe-based confocal laser endomicroscopy - pCLE) is an optical imaging technique that provides high-resolution in vivo imaging and real-time evaluation of urothelial lesions. AIM: To assess the diagnostic capabilities of pCLE in papillary bladder tumors and compare its results with standard pathomorphological study. MATERIALS AND METHODS: A total of 38 patients (27 men, 11 women, aged 41-82 years) with primary bladder tumors diagnosed on the imaging methods were included in the study. For the diagnosis and treatment, all patients underwent transurethral resection (TUR) of the bladder. When a standard white light cystoscopy with assessment of the entire urothelium, 10% sodium fluorescein was administrated intravenously as a contrast dye. pCLE was performed with CystoFlexTMUHD 2.6 mm (7.8 Fr) probe, which was passed through the 26 Fr resectoscope using a telescope bridge to visualize normal and pathological urothelial lesions. A laser with a wavelength of 488 nm and a speed of 8 to 12 frames per second allowed to obtain an endomicroscopic image. These images were compared with standard histopathological analysis using hematoxylin-eosin (H&E) staining of tumor fragments removed during TUR of the bladder. RESULTS: Based on real-time pCLE, 23 patients had a diagnosis of low-grade urothelial carcinoma, while in 12 patients the endomicroscopic picture corresponded to high-grade urothelial carcinoma, 2 patients had typical changes for inflammatory process and 1 case of carcinoma in situ was suspected, which was confirmed by histopathological study. Endomicroscopic images demonstrated clear differences between normal bladder mucosa and high- and low-grade tumors. In the normal urothelium, the larger umbrella cells are located most superficially, followed by smaller intermediate cells, as well as the lamina propria with blood vessels network. In contrast, low-grade urothelial carcinoma is characterized by denser, normal-shaped small cells located superficially than a central fibrovascular core. High-grade urothelial carcinoma exhibits markedly irregular cell architecture and cellular pleomorphism. CONCLUSION: pCLE is a promising new method for in-vivo diagnosing of bladder cancer. Our results show its potential for endoscopic determination of the histological characteristics of bladder tumors and the ability to differentiate between benign and malignant processes, as well as the histological grade of tumor cells.	bladder